Changes in trabecular bone, hematopoiesis and bone marrow vessels in aplastic anemia, primary osteoporosis, and old age: a comparative histomorphometric study.

Retrospective histologic analyses of bone biopsies and of post mortem samples from normal persons of different age groups, and of bone biopsies of age- and sex-matched groups of patients with primary osteoporosis and aplastic anemia show characteristic age dependent as well as pathologic changes including atrophy of osseous trabeculae and of hematopoiesis, and changes in the sinusoidal and arterial capillary compartments. These results indicate the possible role of a microvascular defect in the pathogenesis of osteoporosis and aplastic anemia.

Prognostic significance of glucocorticoid receptor determination in patients with chronic lymphocytic leukemia and immunocytoma--lack of a positive correlation between receptor levels and clinical responsiveness.

Glucocorticoid receptors (GR) have been suggested to have prognostic significance in patients with CLL treated with chemotherapy containing glucocorticoid. In this study, the GR levels in 65 patients with advanced CLL and immunocytoma (clinical stages III and IV according to Rai) were determined by means of a whole cell assay. The median GR-level was 1,920 bs/c with a range from 0 to 9591. The patients were subsequently treated according to a prospective, randomized trial with either a combination of chlorambucil and prednisolone, or with prednimustine. No significant difference in receptor levels was found between responders (median = 1940 bs/c; n = 47) and nonresponders (median = 1950 bs/c; n = 14). To assess the influence of receptor content on prognosis we have analyzed the relationship between GR content and survival time and duration of response. There was no significant difference in duration of response and in survival between those patients with high (greater than 1920 bs/c) and those with low GR levels (less than 1920 bs/c) (log-rank test). Our data suggest that determination of GR provides no reliable indicator for clinical response to regimens with glucocorticoid as a component in patients with CLL and immunocytoma.

The risk of developing breast cancer within the next 5, 10, or 20 years of a woman's life.

BACKGROUND: The lifetime risk of developing breast cancer is a frequently misinterpreted statistic. Risk projections over a shorter time period, conditioned on current age, may be less prone to misconceptions and more relevant to populations at different ages. The purpose of this study was to estimate the risk of developing breast cancer within the next 5, 10, or 20 years for women currently aged 30 to 70 years in California's four major race/ethnic groups. METHODS: Life tables were used to obtain risk estimates based on 1993-1997 breast cancer incidence rates from the California Cancer Registry and statewide mortality rates. RESULTS: For women currently aged 50, the estimated risk of developing invasive breast cancer within 5 years varied from 0.8% (1 in 133) among Hispanics to 1.3% (1 in 75) among Caucasians. Risk estimates within 10 years were 2.9% (1 in 34) among Caucasians, 2.3% (1 in 43) among African Americans, 2.0% (1 in 51) among Asian/Pacific Islanders, and 1.6% (1 in 63) among Hispanics. Within 20 years, estimated risks increased to 6.6% (1 in 15) among Caucasians, 5.0% (1 in 20) among African Americans, 3.9% (1 in 26) among Asian/Pacific Islanders, and 3.7% (1 in 27) among Hispanics. Risk estimates were 8% to 20% higher when in situ tumors were included in the calculations. CONCLUSIONS: Based on these estimates, the baseline risk of developing breast cancer in the next 1 or 2 decades of life varies by race/ethnicity and current age, but may be lower than the risk perceived by most women.

Favorable response of early stage B CLL patients to treatment with IFN-alpha 2.

Since interferon (IFN-alpha) treatment has proven effective in hairy cell leukemia, its evaluation in chronic lymphocytic leukemia (CLL), a cytologically related disease, appeared reasonable. In our study, we have focused on previously untreated, early stage patients who are less than 60 years of age. All patients had less than 50,000 lymphocytes/microL and immunologic analysis revealed a CD20+, IgM+, IgD- phenotype for leukemic B cells in eight of nine patients. Recombinant interferon alpha 2b (IFN-alpha 2) at 5 x 10(6) U was given subcutaneously three times per week for 8 to 16 months. Consistent with earlier reports, side effects were minor with this low-dose protocol. All patients responded with a decrease of WBC count and lymphocyte count; in one patient, splenomegaly resolved such that he moved from Rai stage II to Rai stage I. On the average CD20+ B cells decreased from 14,312 to 3,995 cells/microL, indicating that no complete eradication of the leukemic cells was possible. A partial response, based on a greater than 50% reduction of CD20+ B cells was obtained in five of seven patients analyzed. The increased numbers of CD2+ T lymphocytes decreased in response to interferon treatment in six of seven patients. Furthermore, in a portion of the patients class II antigen expression was enhanced on LeuM3+ monocytes suggesting an in vivo activation of the monocytes by IFN-alpha 2. Immunoglobulin levels were substantially improved in that serum IgG increased by more than 3 g/L in three of seven patients. In one patient, lymphocyte counts increased in spite of continued therapy, whereas all others exhibited no increase of lymphocyte numbers while on therapy. Our study clearly demonstrates effects of IFN-alpha 2 treatment on both the leukemic cells and on the nonleukemic components of the immune system in peripheral blood. Whether IFN-alpha treatment will result in long-term beneficial effects in early stage CLL needs to be evaluated in a larger study.

Increasing trends in the use of breast-conserving surgery in California.

OBJECTIVES: The purpose of this study was to determine temporal trends in breast-conserving surgery in California from 1988 through 1995. METHODS: Logistic regression was used to analyze data on 104,466 cases of early-stage breast cancer reported to the California Cancer Registry. RESULTS: A monotonically increasing trend in breast-conserving surgery was detected after adjustment for age, race/ethnicity, stage at diagnosis, and neighborhood education level. Breast-conserving surgery increased at similar rates among all racial/ethnic groups. Older age, Asian or Hispanic race/ethnicity, late-stage diagnosis, and residence in an undereducated neighborhood were factors associated with lower use of breast-conserving surgery. CONCLUSIONS: Although disparities are evident, use of breast-conserving surgery increased steadily in all groups examined in this study.

Detection of haematologic and nonhaematologic cancer by bone biopsy.

A retrospective study was carried out to test the efficacy of routine bone marrow biopsies for the diagnosis, classification, and prognosis of different forms of neoplastic involvement. Trephine and needle biopsies of the iliac crest of 3,626 patients with haematologic and 838 patients with nonhaematologic neoplasias were embedded without prior decalcification. 43 histologic variables were evaluated in 3-millimicrons sections of each biopsy, stained by five different techniques. The incidence of bone marrow involvement, in decreasing order of frequency, was as follows: plasmacytoma 55% and 95% of 428 cases, malignant lymphoma 37% and 79% of 1.112 cases, metastatic carcinoma 20% and 63% of 838 cases, and Hodgkin disease 3% and 28% of 772 cases each without and with manifest systemic dissemination. In the group of the metastatic carcinomas, there was a striking incidence of bone marrow involvement--82%--due to occult primary tumours. From a comparison of these figures with those reported in the literature, it is concluded that the large variations in positive and negative results are due to 1) differences in the size and the preparation of the specimens, 2) extent of the neoplastic dissemination at the time of the biopsy, and 3) the incidence of bone marrow involvement characteristic for a particular type of neoplasia. In addition, a subclassification of the chronic myeloproliferative disorders is proposed; it is based on histologic criteria whose prognostic relevance was tested and demonstrated by statistical analysis of the survival rates. The high incidence of detection reported in this study in patients without other evidence of systemic spread, or even in patients with occult neoplasias, provides a strong justification for the use of bone marrow biopsy as a primary diagnostic tool as well as a staging procedure, in both haematologic and nonhaematologic cancer.

Sociodemographic factors associated with prostatectomy utilization and concordance with the physician data query for prostate cancer (United States).

OBJECTIVES: Data from the California Cancer Registry were used to model the effect of race/ethnicity, census-derived socioeconomic status (SES), age, year, and stage at diagnosis on prostatectomy utilization in men diagnosed with prostate cancer from 1990 through 1993. Treatment received was compared with the National Cancer Institute's Physician Data Query (PDQ) to evaluate concordance. METHODS: Odds ratios (OR) and 95% confidence intervals (CI) were estimated to assess the likelihood of (a) receiving a prostatectomy and (b) receiving a treatment in concordance with the PDQ. Non-concordance was defined as a prostatectomy performed on a patient who was either diagnosed with AJCC stage III or IV prostate cancer, or was older than 70 years. All other treatments were considered compliant with the PDQ. RESULTS: Regardless of the stage at diagnosis, men who were younger and lived in a neighborhood with higher income and education levels were the most likely to receive a prostatectomy as opposed to other treatments. Black men were the least likely to be treated with prostatectomy (OR = 0.6, CI = 0.5-0.6), and the differential was evident within all income levels examined. With respect to the PDQ, black men were 1.4 times more likely to receive concordant treatment than white men (OR = 1.4, CI = 1.3-1.5). CONCLUSIONS: California black men are receiving less aggressive treatment (that is more concordant with the PDQ) when diagnosed with prostate cancer.

[Interferon alfa-2B in chronic lymphatic leukemia of the B-cell type]. / Interferon alpha-2b bei chronischer lymphatischer Leukämie vom B-Zell-Typ.

In a clinical phase II study nine patients (five men and four women; mean age 48 [42-58] years) in an early stage of chronic lymphatic leukaemia (CLL) of the B-cell type were treated with recombinant alpha-2b interferon (IFN alpha-2b), initially at a dosage of 5 mega units subcutaneously three times weekly, but in some cases reduced to 2.5 or raised to 10 mega units. Duration of treatment has been 15-36 months. Through-flow cytometry in seven patients demonstrated a definite fall in circulating B1-positive lymphocytes. Lasting partial remission (duration of 106-134 weeks) was achieved in four patients, in a further four the condition remained stable. A recurrence was noted in the patient with the initially highest lymphocyte count (52,000/microliters) after 28 weeks, control being achieved only after 64 weeks of chemotherapy. Side effects were flu'-like symptoms and (in two instances) depression. In three patients there was a clear rise in serum immunoglobulin concentrations as sign of IFN alpha-2b-induced increased immune response, while in four HLA-DR expression on monocytes was doubled. It is concluded that early treatment of CLL with IFN alpha-2b may delay the onset of necessary chemotherapy, any antibody-deficiency may be improved and survival time may ultimately be lengthened.

[Multilocular, immature-cell myelogenous infiltrates of the skin in a patient with chronic myelomonocytic leukemia following polycythemia vera and anti-cardiolipin syndrome]. / Multilokuläre, unreifzellige myelogene Infiltrate der Haut bei einer Patientin mit chronisch-myelomonozytärer Leukämie nach Polyzythaemia vera und Anticardiolipin-Syndrom.

We report a 65-year-old patient presenting with disseminated, reddish, thick infiltrates and nodules during chronic myelomonocytic leukaemia and anticardiolipin syndrome. Histological and immunohistochemical investigations revealed immature myelogenous skin infiltrates.

Lead levels in the household environment of children in three high-risk communities in California.

To assess environmental lead contamination in the household environment of children in high-risk areas of California, three urban locations were surveyed by the California Department of Health Services. Plant, soil, and dust lead levels were measured and a questionnaire was administered. This survey estimates that 3 million homes in California (27%) may have exterior paint lead levels > or = 5000 ppm, and 1.3 million homes (12%) may have interior paint lead levels > or = 5000 ppm. The highest concentrations of lead in paint were found on exterior surfaces and, for homes built between 1920 and 1959, on trim. Age of housing was the best predictor of lead in soil and dust; homes built before 1920 were 10 times more likely to have soil lead levels > or = 500 ppm compared to post-1950 homes. Most of the variability in dust lead levels could not be explained by factors measured in this survey. Sources of lead in the home were more highly correlated with lead dust concentration levels than they were with lead dust loading levels. Households with members reporting a lead job were twice as likely to have high dust lead levels compared to households with no one reporting a lead job. The significant differences in dust lead concentration levels between communities were not reflected in differences in dust lead loading levels. Measuring dust lead loading levels does not appear to be a meaningful sampling method for risk assessment in the context of prioritizing abatement.

Decreased production of TNF and IL-6 in whole blood of CLL patients.

Monocyte derived cytokines, tumor necrosis factor (TNF) and interleukin-6 (IL-6), were determined in cell free plasma after stimulation of heparinized whole blood from chronic lymphocytic leukemia (CLL) patients with lipopolysaccharide (LPS) at 1 microgram/ml for 6 hr. Compared to control donors (390 U/ml), CLL patients in average had eight-fold lower levels of TNF bioactivity (50 U/ml). The depressed levels were observed over a wide range of LPS concentrations (0.01 to 10 micrograms/ml). Furthermore, after stimulation with S. aureus bacteria, CLL samples gave three-fold lower levels, as well. TNF levels were not decreased because of defective bioactivity of TNF, since strongly reduced levels of TNF protein were also detected in an immunoassay. Finally, interleukin-6 levels after LPS stimulation were decreased threefold. Flow cytometry analysis with CD14 antibodies demonstrated comparable numbers of monocytes for control donors and CLL patients (698 +/- 802 and 427 +/- 267, respectively). This suggests that deficient cytokine production was not due to a reduction in monocyte number, but rather to a functional impairment. The deficiency in cytokine production observed after ex vivo stimulation of whole blood from CLL patients suggests that in vivo during bacterial infection, CLL patients will exhibit an inappropriate response as well.

Cancer among Hispanic children in California, 1988-1994: comparison with non-Hispanic white children.

BACKGROUND: There has been a perception that California Hispanic children have an unusually high cancer incidence rate, but to the authors' knowledge the only information regarding cancer rates in this population has been the tabular data published in reports issued by the California Department of Health Services. The California Cancer Registry has collected data regarding all cancers diagnosed in California since 1988. METHODS: Data regarding all invasive cancers diagnosed in California Hispanic children age <15 years during the 7-year period 1988-1994 were analyzed. Cancers were grouped according to the International Classification for Childhood Cancers. Age-adjusted and age specific incidence rates were compared with the corresponding incidence rates among non-Hispanic white children. RESULTS: Based on available demographic information, the overall incidence rate of cancer was approximately 7% lower among California children classified as Hispanic than among non-Hispanic white children. Hispanic children had higher incidence rates of lymphoid leukemia and gonadal germ cell tumors and a lower incidence rate of astrocytomas and carcinomas than non-Hispanic white children. CONCLUSIONS: These data do not confirm the perception that California Hispanic children have an unusually high cancer incidence rate but there were notable differences between Hispanic and non-Hispanic white children with regard to the incidence rates of certain cancers. The perception may be due in part to the fact that childhood malignancies represented 3.1% of all cancers diagnosed among Hispanics but only 0.5% of all cancers diagnosed among non-Hispanic whites. This is explained by the lower incidence rate of cancer among California Hispanic adults than among non-Hispanic white adults and the difference in the age distribution of the two populations.